VTE Prevention Following Total Hip and Knee Arthroplasty

Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban and Aspirin to Aspirin Alone Following Total Hip and Knee Arthroplasty (EPCATIII)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04075240

Acronym

EPCATIII

Enrollment

5429

Registered

2019-08-30

Start date

2021-02-04

Completion date

2026-06-10

Last updated

2026-06-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Venous Thromboembolism

Keywords

total hip and knee arthroplasty

Brief summary

Consented patients undergoing elective total hip and total knee arthroplasty will be randomized to receive either aspirin alone or aspirin and rivaroxaban for prevention of venous thromboembolism.

Detailed description

Aspirin and rivaroxaban prevent venous thromboembolism (VTE) via different mechanisms. Aspirin is significantly cheaper than rivaroxaban. Aspirin in combination with rivaroxaban was shown to be safe and efficacious in a non-inferiority trial (EPCATII) when compared to rivaroxaban alone. This study will assess if aspirin alone is non-inferior to rivaroxaban and aspirin in the prevention of venous thromboembolism.

Interventions

DRUGRivaroxaban 10 MG and acetylsalicylic acid 81 mg

Starting post op, rivaroxaban (5 days) followed by aspirin (9 days for TKA; 30 days for THA)

DRUGacetylsalicylic acid 81 mg

Starting post op, aspirin for 9 days for TKA and 30 days for THA

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

over-encapsulated rivaroxaban/ASA

Intervention model description

randomized, controlled, double-blind

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Patients undergoing elective THA/TKA at the participating institutions will be potentially eligible for this study 2. Written informed consent in accordance with federal, local and institutional guidelines

Exclusion criteria

1. Previous documented VTE (proximal DVT or any PE) 2. Hip or lower limb fracture in the previous three months, not related to present surgery 3. Metastatic cancer 4. Life expectancy less than 6 months 5. History of major bleeding that in the judgment of the investigator precludes use of anticoagulant prophylaxis 6. History of aspirin allergy, active peptic ulcer disease or gastritis that in the judgment of investigator precludes use of aspirin 7. History of significant hepatic disease or any other condition that in the judgment of the investigator precludes the use of rivaroxaban 8. Creatinine clearance less than 15 ml per minute 9. Pre-operative platelet count less than 100 x 109 /L 10. Need for long-term anticoagulation due to a pre-existing co-morbid condition or due to the development of VTE following surgery but prior to randomization 11. Received anticoagulation post operatively 12. Bilateral THA/TKA or simultaneous hip and knee arthroplasty 13. Major surgical procedure within the previous 3 months 14. Requirement for major surgery post arthroplasty within a 90 day period 15. Chronic daily aspirin use with dose greater than 100 mg a day 16. Women of childbearing potential who are not abstinent or do not use effective contraception or are breast-feeding throughout the study drug period 17. Unwilling or unable to give consent 18. Previous participation in the EPCAT III study 19. Under 18 years of age 20. Concomitant use of drugs that are strong inhibitors of P-gp AND CYP3A4 (e.g., systemic treatment with ketoconazole, itraconazole, or ritonavir) or strong inducers of P-gp AND CYP3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) 21. Known allergy to food dye

Design outcomes

Primary

Measure	Time frame	Description
Venous thromboembolism	90 days	symptomatic proximal deep vein thrombosis or pulmonary embolism
Bleeding	90 days	major and clinically relevant, non-major bleeds

Secondary

Measure	Time frame	Description
Survival	90 days	all cause death
Cost-effectiveness	90 days	quantitatively describe the costs of symptomatic thromboembolism events and major bleeding episodes

Countries

Canada

Contacts

PRINCIPAL_INVESTIGATORSudeep P Shivakumar, MD

Dalhousie University/Nova Scotia Health Authority

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jul 14, 2026